Search for genetic variations conferring risk of schizophrenia by exome sequencing in a Japanese multiplex pedigree

• Project/Area Number: 24791203
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: NUNOKAWA Ayako 新潟大学, 医歯(薬)学総合研究科, 非常勤講師 (90584607)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 統合失調症 / 全エクソン解析

Research Abstract

To identify rare penetrant risk variations for schizophrenia, we performed exome sequencing in a Japanese multiplex schizophrenia pedigree. We obtained DNA from six affected, eight unaffected and one unknown affection status individuals in the pedigree. A total of 302,005 sequence variations were called in the exome sequencing of two affected and one unaffected individuals.We selected seven putatively functional missense variations as candidate risk variations for schizophrenia. Among four variations confirmed by Sanger sequencing, V1525M variation in the UNC13B gene was most strongly cosegregated with schizophrenia in the pedigree. These results suggest that the UNC13B V1525M variation is a potential risk variant for schizophrenia.

Research Products

• [Journal Article] A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population (2014)
  • Author(s): Watanabe, Y., Hishimoto, A., Shibuya, M., Nunokawa, A., Kaneko, N., Igeta, Egawa, J., Mouri, K., Sora, I., Someya, T.
  • Journal Title: Psychiatry Research Volume: 215 Issue: 3 Pages: 801-802
  • DOI: 10.1016/j.psychres.2013.12.029
  • Peer Reviewed
• [Journal Article] Interleukin 1 beta gene and risk of schizophrenia : detailed case-control and family-based studies and an updated meta-analysis (2014)
  • Author(s): Shibuya, M., Watanabe, Y., Nunokawa, A., Egawa, J., Kaneko, N., Igeta, H., Someya, T.
  • Journal Title: Human Psychopharmacology : Clinical and Experimental Volume: 29 Issue: 1 Pages: 31-37
  • DOI: 10.1002/hup.2365
  • Peer Reviewed
• [Journal Article] Association analysis of putative cis-acting polymorphisms of interleukin-19 gene with schizophrenia (2014)
  • Author(s): Okazaki, S., Watanabe, Y., Hishimoto, A., Sasada, T., Mouri, K., Shiroiwa, K., Eguchi, N., Ratta-Apha, W., Otsuka, I., Nunokawa, A., Kaneko, N., Shibnuya. M., Someya, T., Shirakawa, O., Sora, I.
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume: 50 Pages: 151-156
  • DOI: 10.1016/j.pnpbp.2013.12.006
  • Peer Reviewed
• [Journal Article] An evaluation of association between a novel hippocampal biology related SNP (rs7294919) and schizophrenia (2013)
  • Author(s): Liu, J., Numata, S., Ikeda, M., Watanabe, Y., Zheng, X., Luo, X., Kinoshita, M., Nunokawa, A., Someya, T., Ohmori, T., Bei, J., Chong, S., Lee, J., Li, Z., Liu, J., Iwata, N., Shi, Y., Li, M., Su, B
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e80696-e80696
  • DOI: 10.1371/journal.pone.0080696
  • Peer Reviewed
• [Journal Article] Replication in a Japanese population that a MIR30E gene variation is associated with schizophrenia (2013)
  • Author(s): Watanabe, Y., Iijima, Y., Egawa, J., Nunokawa, A., Kaneko, N., Arinami, T., Ujike, H., Inada, T., Iwata, N., Kunugi, H., Itokawa, M., Sasaki, T., Ozaki, N., Hashimoto, R., Shibuya, M., Igeta, H., Someya, T.
  • Journal Title: Schizophrenia Research Volume: 150 Issue: 2-3 Pages: 596-597
  • DOI: 10.1016/j.schres.2013.08.028
  • Peer Reviewed
• [Journal Article] Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population (2013)
  • Author(s): Ikeda M, Aleksic B, Yamada K, Iwayama-Shigeno Y, Matsuo K, Numata S, Watanabe Y, Ohnuma T, Kaneko T, Fukuo Y, Okochi T, Toyota T, Hattori E, Shimodera S, Itakura M, Nunokawa A, Shibata N, Tanaka H, Yoneda H, Arai H, Someya T, Ohmori T, Yoshikawa T, Ozaki N, Iwata N
  • Journal Title: Mol Psychiatry Volume: 18(6) Issue: 6 Pages: 636-638
  • DOI: 10.1038/mp.2012.74
  • Peer Reviewed
• [Journal Article] Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population (2013)
  • Author(s): Egawa, J., Nunokawa, A., Shibuya, M., Watanabe, Y., Kaneko, N., Igeta, H., Someya, T.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 67 Issue: 4 Pages: 277-279
  • DOI: 10.1111/pcn.12047
  • Peer Reviewed
• [Journal Article] ssociation of the BDNF C270T polymorphism with schizophrenia: An updated meta-analysis (2013)
  • Author(s): Watanabe, Y., Nunokawa, A., Someya, T.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 67 Issue: 2 Pages: 123-125
  • DOI: 10.1111/pcn.12018
  • Peer Reviewed
• [Journal Article] Oxytocin receptor (OXTR) gene and risk of schizophrenia : Case-control and family-based analyses and meta-analysis in a Japanese population (2012)
  • Author(s): Watanabe, Y., Kaneko, N., Nunokawa, A., Shibuya, M., Egawa, J., Someya, T.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 66 Issue: 7 Pages: 622-622
  • DOI: 10.1111/j.1440-1819.2012.02396.x
  • Peer Reviewed
• [Journal Article] Supportive evidence for the association between the Gln2Pro polymorphism in the SIGMAR1 gene and schizophrenia in the Japanese population : A case-control study and an updated meta-analysis (2012)
  • Author(s): Watanabe, Y., Nunokawa, A., Kaneko, N., Shibuya, M., Egawa, J., Someya, T.
  • Journal Title: Schizophrenia Research Volume: 141 Issue: 2-3 Pages: 279-280
  • DOI: 10.1016/j.schres.2012.06.043
  • Peer Reviewed
• [Journal Article] Case-control study and meta-analysis of Ser311Cys polymorphism in the DRD2 gene demonstrate lack of association with risk of for schizophrenia in the Japanese population (2012)
  • Author(s): Watanabe, Y., Nunokawa, A., Kaneko, N., Shibuya, M., Egawa, J., Fukui, N., Someya, T.
  • Journal Title: Genetics and Molecular Research Volume: 11 Issue: 2 Pages: 1142-1145
  • DOI: 10.4238/2012.april.27.13
  • Peer Reviewed
• [Journal Article] A two-stage case-control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population (2012)
  • Author(s): Watanabe Y, Egawa J, Iijima Y, Nunokawa A, Kaneko N, Shibuya M, Arinami T, Ujike H, Inada T, Iwata N, Tochigi M, Kunugi H, Itokawa M, Ozaki N, Hashimoto R, Someya T
  • Journal Title: Schizophr Res Volume: 137(1-3) Issue: 1-3 Pages: 264-266
  • DOI: 10.1016/j.schres.2012.01.034
  • Peer Reviewed
• [Journal Article] A detailed association analysis between the tryptophan hydroxylase 2 (TPH2) gene and autism spectrum disorders in a Japanese population. (2012)
  • Author(s): 江川 純
  • Journal Title: Psychiatry Research Volume: 196 Pages: 320-322
  • Peer Reviewed
• [Journal Article] Case-control study and meta-analysis of Ser311Cys polymorphism in the DRD2 gene demonstrate lack of association with risk for schizophrenia in the Japanese population (letter). (2012)
  • Author(s): 渡部 雄一郎
  • Journal Title: Genetics and Molecular Research Volume: 11 Pages: 1142-1145
  • Peer Reviewed
• [Presentation] Supportive evidence for the association between the Gln2Pro polymorphism in the sigma non-opioid intracellular receptor 1 gene and schizophrenia in the Japanese population (2013)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Shibuya M, Egawa J, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto
  • Year and Date: 2013-06-25
• [Presentation] Case-control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population (2013)
  • Author(s): Nunokawa A, Watanabe Y, Egawa J, Kaneko N, Shibuya M, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto
  • Year and Date: 2013-06-24
• [Presentation] Case-control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population (2013)
  • Author(s): Nunokawa A, Watanabe Y, Egawa J, Kaneko N, Shibuya M, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都
• [Presentation] Supportive evidence for the association between the Gln2Pro polymorphism in the sigma non-opioid intracellular receptor 1 gene and schizophrenia in the Japanese population (2013)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Shibuya M, Egawa J, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都
• [Presentation] オキシトシン受容体遺伝子と統合失調症の関連解析 (2012)
  • Author(s): 井桁裕文, 渡部雄一郎, 金子尚史, 布川綾子, 澁谷雅子, 江川純, 染矢俊幸
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-09-30
• [Presentation] Case-control study and meta-analysis did not confirm an association between DRD2 Ser311Cys and schizophrenia in the Japanese population (2012)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Shibuya M, Egawa J, Fukui N, Igeta H, Someya T
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry and 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe
• [Presentation] A case-control study and meta-analysis of association between a common copy number variation of the glutathione S-transferase mu 1 (GSTM1) gene and schizophrenia (2012)
  • Author(s): Nunokawa A, Watanabe Y, Kaneko N, Shibuya M, Igeta H, Someya T
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry and 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe
• [Presentation] A case-control study and meta-analysis of association between a common copy number variation of the glutathione S-transferase mu1 (GSTM1)gene and schizophrenia. (2012)
  • Author(s): 布川 綾子
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry and 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
• [Presentation] Case-conrtol study and meta-analysis did not confirm an association between DRD2 Ser311Cys and schizophrenia in the Japanese population. (2012)
  • Author(s): 渡部 雄一郎
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry and 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
• [Presentation] Rare missense variations of TPH2 and risk of autism: Exon resequensing and association analysis. (2012)
  • Author(s): 江川 純
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry and 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
• [Presentation] オキシトシン受容体遺伝子と統合失調症の関連解析 (2012)
  • Author(s): 井桁 裕文
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）